OVERALL DESCRIPTION (Provided by the applicant) The overall mortality following acute renal failure has remained at approximately 50%. It is unlikely that this high mortality and associated cost will be reduced until we have a better understanding of the cellular and molecular mechanisms of cell injury and recovery. This program project grant application represents a multidisciplinary collaborative effort among basic scientists and clinician scientists around a central theme of elucidating the cellular and molecular basis of rental tubular epithelial cell injury, including concepts that have been learned from the study of apoptosis. Participating in the projects are members of six departments (Medicine, Pathology, Microbiology & Immunology, Geriatrics, Biochemistry and Physiology) and include several cell biologists with expertise with in vitro and in vivo models of acute renal failure (Shah, Portilla, Walker, Safirstein), investigators with expertise in molecular biology (Crew, Portilla, Haun, Price), clinician scientist who is a renal pathologist (Walker), and biochemists with particular expertise in protein purification (Kaushal, Basnakian). Additional strengths include: 1. Some of the original observations of the relevance of the concepts learned from the study of apoptosis to renal tubular injury were reported by participants in this application. 2. The program director, project leaders as well as other co-investigators have a history of professional association and publishing collaborative studies. The laboratories and offices of all project leaders are located in close proximity to each other allowing ready access and interaction between the participants. 3. Several of the investigators participating in the program project as well as other investigators at the institution in the Departments of Pharmacology, Physiology and the Division of Nephrology have ongoing projects that are directly related to the central theme of this grant application which further strengthens the environment to pursue the goals of the application. The program has attained a critical mass of investigators to address the pathogenesis of acute renal failure in a multifaceted, synergistic fashion thus matching the overall stated objectives of the program project guidelines.